Neurobiologic Alterations in Bariatric Surgery: Taste Response and Weight Loss

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): I am a junior faculty member in the Department of Surgery at the Johns Hopkins University School of Medicine, and a Ph.D. candidate in Clinical Investigation from the Johns Hopkins Bloomberg School of Public Health. My previous work has focused on brain dopamine (DA) alterations in obese patients following gastric bypass. The objective of this mentored research project is to investigate alterations in the neurobiology of taste preference induced by bariatric surgery, and to explore the relationship of taste responsiveness to successful long-term weight loss. While conducting this study I will enhance my research knowledge and skills through formal coursework in nutritional epidemiology, neuroscience, and neuroimaging and through directed research mentorship by a team of experts in behavioral neuroscience, psychiatry, nutrition, epidemiology and surgery. Obesity has reached epidemic proportions and the most successful method of sustained weight loss is bariatric surgery. Despite the indisputable effectiveness of bariatric surgery in the aggregate, there remains significant inter-individual variability in treatment response. The mechanisms by which these bariatric procedures lead to weight loss in humans are only partially understood. A better understanding of the underlying mechanisms of weight loss in the bariatric surgical patient will allow for improved treatments and outcomes. My hypothesis is that weight loss after bariatric surgery is due in part to alterations in food preferences and changes in taste. I plan to investigate taste responses to varying concentrations of sucrose and fat-containing stimuli before and after vertical sleeve gastrectomy (VSG, n=20) or Roux-en Y gastric bypass (RYGB, n=20), as well as in a control group using diet-induced weight loss (n=20). Participants will be assessed at 2 weeks and 1 week prior, and 2 weeks, 3 months, 6 months, and 12 months after the intervention. Taste preferences to varying levels of sucrose and fat-containing stimuli will be measured, and validated questionnaires used to qualitatively determine reward sensitivity, binge eating behavior, and impulsivity. Functional magnetic resonance imaging (fMRI) will be performed to assess neurobiologic changes in reward regions of the brain. Blood-oxygen-level- dependent (BOLD) fMRI signaling will be used to assess DA-mediated reward circuitry (e.g. striatum) in response to sucrose and fat-containing stimuli at one week before and two weeks after surgery. These studies will complement my previous work on the relation of dopamine-based reward regions and obesity, enhancing our understanding of the mechanisms involved in feeding behavior. I expect that patients who undergo a bariatric surgical intervention will have a significant change in taste preference immediately following surgery, but that this change will not persist indefinitely. We will define this period of taste change and determine the relationship between weight loss, taste alterations, and specific neuroanatomical brain activity. I believe that this research will correlate pre-operative taste preference with long term weight loss outcome. The clinical implications of this research include improved weight loss outcomes from bariatric surgery.